Condensin I recruitment and uneven chromatin condensation precede mitotic cell death in response to DNA damage.

Abstract	Mitotic cell death (MCD) is a prominent but poorly defined form of death that stems from aberrant mitosis. One of the early steps in MCD is premature mitosis and uneven chromatin condensation (UCC). The mechanism underlying this phenomenon is currently unknown. In this study, we show that DNA damage in cells with a compromised p53-mediated G2/M checkpoint triggers the unscheduled activation of cyclin-dependent kinase 1 (Cdk1), activation and chromatin loading of the condensin I complex, and UCC followed by the appearance of multimicronucleated cells, which is evidence of MCD. We demonstrate that these processes engage some of the players of normal mitotic chromatin packaging but not those that drive the apoptotic chromatin condensation. Our findings establish a link between the induction of DNA damage and mitotic abnormalities (UCC) through the unscheduled activation of Cdk1 and recruitment of condensin I. These results demonstrate a clear distinction between the mechanisms that drive MCD-associated and apoptosis-related chromatin condensation and provide mechanistic insights and new readouts for a major cell death process in treated tumors.
Authors	Michael Blank, Yaniv Lerenthal, Leonid Mittelman, Yosef Shiloh
Journal	The Journal of cell biology (J Cell Biol) Vol. 174 Issue 2 Pg. 195-206 (Jul 17 2006) ISSN: 0021-9525 [Print] United States
PMID	16847100 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Cell Cycle Proteins Chromatin Chromosomal Proteins, Non-Histone DNA-Binding Proteins Multiprotein Complexes Nuclear Proteins cohesins condensin complexes CDC2 Protein Kinase Adenosine Triphosphatases
Topics	Adenosine Triphosphatases (metabolism) CDC2 Protein Kinase (metabolism) Cell Cycle Proteins (metabolism) Cell Death Cell Nucleolus (metabolism) Chromatin (genetics, metabolism) Chromosomal Proteins, Non-Histone (metabolism) DNA Damage DNA-Binding Proteins (metabolism) Enzyme Activation G2 Phase (genetics) HCT116 Cells HeLa Cells Humans Mitosis Models, Genetic Multiprotein Complexes (metabolism) Nuclear Proteins (metabolism) Protein Transport Tumor Cells, Cultured

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